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α 1-antitrypsin enhances insulin secretion and prevents cytokine-mediated apoptosis in pancreatic β-cells.

In English

Författare

Summary, in English

α1-antitrypsin (AAT) is a serine protease inhibitor, which recently has been shown to prevent type 1 diabetes (T1D) development, to prolong islet allograft survival and to inhibit β-cell apoptosis in vivo. It has also been reported that T1D patients have significantly lower plasma concentrations of AAT suggesting the potential role of AAT in the pathogenesis of T1D. We have investigated whether plasma-purified AAT can affect β-cell function in vitro. INS-1E cells or primary rat pancreatic islets were used to study the effect of AAT on insulin secretion after glucose, glucagon-like peptide-1 (GLP-1) and forskolin stimulation and on cytokine-mediated apoptosis. The secreted insulin and total cyclic AMP (cAMP) were determined using radioimmunoassay and apoptosis was evaluated by propidium iodide staining followed by FACS analysis. We found that AAT increases insulin secretion in a glucose-dependent manner, potentiates the effect of GLP-1 and forskolin and neutralizes the inhibitory effect of clonidine on insulin secretion. The effect of AAT on insulin secretion was accompanied by an increase in cAMP levels. In addition, AAT protected INS-1E cells from cytokine-induced apoptosis. Our findings show that AAT stimulates insulin secretion and protects β-cells against cytokine-induced apoptosis, and these effects of AAT seem to be mediated through the cAMP pathway. In view of these novel findings we suggest that AAT may represent a novel anti-inflammatory compound to protect β-cells under the immunological attack in T1D but also therapeutic strategy to potentiate insulin secretion in type 2 diabetes (T2D).

Avdelning/ar

Publiceringsår

2010

Språk

Engelska

Sidor

185-189

Publikation/Tidskrift/Serie

Islets

Volym

2

Issue

3

Dokumenttyp

Artikel i tidskrift

Förlag

Landes Bioscience

Ämne

  • Endocrinology and Diabetes

Nyckelord

  • cytokines
  • insulin secretion
  • apoptosis
  • AAT
  • GLP-1
  • beta-cells
  • islets

Status

Published

Forskningsgrupp

  • Diabetes - Immunovirology
  • Islet cell physiology
  • Chronic Inflammatory and Degenerative Diseases Research Unit

ISBN/ISSN/Övrigt

  • ISSN: 1938-2022